Clinical Trials /

Study of Erlotinib and Metformin in Triple Negative Breast Cancer

NCT01650506

Description:

Extended phase 1 trial of combined metformin and erlotinib in advanced triple negative breast cancer patients. The goals of the study are to establish the maximum tolerated combined dosing of erlotinib and metformin as well as deciding if there is a potential clinical utility of the combination in treating patients with triple negative breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of Erlotinib and Metformin in Triple Negative Breast Cancer
  • Official Title: Phase I Study of Erlotinib and Metformin in Triple Negative Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: AAAF3743
  • NCT ID: NCT01650506

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
MetforminGlucophageErlotinib + Metformin
ErlotinibTarcevaErlotinib + Metformin

Purpose

Extended phase 1 trial of combined metformin and erlotinib in advanced triple negative breast cancer patients. The goals of the study are to establish the maximum tolerated combined dosing of erlotinib and metformin as well as deciding if there is a potential clinical utility of the combination in treating patients with triple negative breast cancer.

Detailed Description

      Breast cancer has several different subtypes based upon measurement of expression of proteins
      found on the surface of the cancer cells. Cancers that lack expression of three of these
      proteins, namely the estrogen receptor, progesterone receptor, and human epidermal growth
      factor receptor 2 (HER2), are termed triple negative. By studying the molecular attributes of
      breast cancer cells from a large group of breast cancer patients, a profile of markers
      enriched in triple negative breast cancers (TNBC) was discovered. This profile includes loss
      of expression of the protein, Phosphatase and Tensin homolog (PTEN), increased expression of
      the protein, epidermal growth factor receptor (EGFR), and disruption of the cells ability to
      repair DNA. These alterations also allow the tumor to thrive and likely evade treatment.
      Observation has been made that the drug combination of metformin and erlotinib can inhibit
      triple negative cells with these alterations. A clinical trial will be conducted to test the
      ability of patients to tolerate the treatment (Phase I trial). This trial will be available
      to triple negative breast cancer patients with metastatic disease. Other goals of the study
      will be to confirm that the drugs are working properly and whether or not there are enough
      responses to the treatment to warrant additional studies. If the treatment proves to be
      effective, even if only in a subset of triple negative patients, future studies will focus on
      validating biomarkers that can identify patients that will respond to the drug combination,
      as well as discovering how cells become resistant to the treatment. The research has the
      potential to advance a new effective treatment for a highly lethal disease and thus could
      prolong patient survivals while maintaining a high quality of life.
    

Trial Arms

NameTypeDescriptionInterventions
Erlotinib + MetforminExperimentalThis is a single arm phase 1 study. All patients will receive erlotinib and metformin.
  • Metformin
  • Erlotinib

Eligibility Criteria

        Inclusion Criteria:

          -  Confirmed pathologic diagnosis of triple negative breast cancer, OR Prior diagnosis of
             ER or P-R positive breast cancer [HER2 negative] that is demonstrated to be both ER
             and P-R negative (no or rare staining) on the patient's most recent biopsy.

          -  Patients with measurable or non-measurable metastatic disease (RECIST 1.1).

          -  At least one prior treatment for metastatic disease.

          -  Availability of adequate tumor tissue for exploratory analysis and plan to obtain the
             material.

          -  Patients must have recovered from the acute toxic effects of all prior chemotherapy,
             immunotherapy, or radiotherapy prior to entering this study. No chemotherapy or
             radiotherapy may be given within 2 weeks prior to the start of protocol treatment.

          -  Patients must be ≥ 18 and < 80 years old.

          -  Performance Status: Eastern Cooperative Oncology Group (ECOG) 0-2.

          -  Life expectancy of greater than 12 weeks.

          -  Patients must have recovered from uncontrolled intercurrent illness including, but not
             limited to, ongoing or active infection, symptomatic congestive heart failure,
             unstable angina pectoris or cardiac arrhythmia.

          -  Required Laboratory Values: Absolute neutrophil count (ANC) ≥1,250/mm3, platelets
             ≥75,000/mm3, hemoglobin ≥8.5 g/dL, total bilirubin ≤1.5 x ULN, Aspartate
             Aminotransferase (AST)/Alanine Aminotransferase (ALT) ≤3.0 x ULN, alkaline phosphatase
             ≤2.5 x ULN, Patients must have either a normal serum creatinine (<= IULN) OR estimated
             creatinine clearance ≥ 60 ml/min (Cockcroft-Gault formula) within 14 days prior to
             registration.

          -  Concomitant Medications: Erlotinib is primarily metabolized by CYP3A4. Patients CANNOT
             be receiving enzyme-inducing or enzyme inhibiting agents listed here: Inhibitors:
             Amiodarone, Amprenavir, Atazanavir, Chloramphenicol, Clarithromycin, Conivaptan,
             Cyclosporine, Darunavir, Dasatinib, Delavirdine, Diltiazem, Erythromycin, Fluconazole,
             Fluoxetine, Fluvoxamine, Fosamprenavir, Imatinib, Indinavir, Isoniazid, Itraconazole,
             Ketoconazole, Lapatinib, Miconazole, Nefazodone, Nelfinavir, Posaconazole, Ritonavir,
             Quinupristin, Saquinavir, Tamoxifen, Telithromycin, Troleandomycin, Verapamil,
             Voriconazole. Inducers: Aminoglutethimide, Bexarotene, Bosentan, Carbamazepine,
             Efavirenz, Fosphenytoin, Griseofulvin, Modafinil, Nafcillin, Nevirapine,
             Oxcarbazepine, Phenobarbital, Phenytoin, Primidone, Rifabutin, Rifampin, Rifapentine,
             St. John's wort, Sulfadimidine, Sulfinpyrazone, Troglitazone, Troleandomycin. All
             concomitant medications must be recorded.

          -  Sexually Active Patients: For all sexually active patients, the use of adequate
             contraception (hormonal or barrier method of birth control) will be required prior to
             study entry and for the duration of study participation. The non-pregnant status will
             be determined in all women of childbearing potential.

          -  Patients must have signed an approved informed consent.

        Exclusion Criteria:

          -  Active central nervous system (CNS) disease

             a. Subjects with a history of CNS metastases or cord compression are allowable if they
             have been clinically stable for at least 6 weeks since completion of definitive
             treatment, are off steroids (if the steroids were part of the CNS disease treatment),
             and in the case of brain metastases, have stable or improved imaging at least 6 weeks
             after completion of their definitive treatment.

          -  Any serious medical or psychiatric illness that would prevent either the giving of
             informed consent or the receipt of treatment.

          -  Patients pregnant or nursing.

          -  Patients who have used tobacco or nicotine products or medications within the last
             three months given their significant effect on erlotinib drug levels.

          -  Diabetes. Defined as HgbA1C ≥ 6.5%.

          -  Prior metformin treatment OR EGFR targeted therapy.

          -  Rapidly progressive disease as judged by the investigator (Examples include rapidly
             deteriorating performance status or symptomatic lymphangitic spread).

          -  Patient has any condition associated with increased risk of metformin-associated
             lactic acidosis (e.g. congestive heart failure defined as New York Heart Association
             (NYHA) Class III or IV functional status, history of acidosis of any type; habitual
             intake of 3 or more alcoholic beverages per day).
      
Maximum Eligible Age:79 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:The maximum tolerated dose of metformin in combination with a fixed dose of 150 mg erlotinib daily
Time Frame:Up to 5 weeks
Safety Issue:
Description:The highest dose of a treatment that does not cause unacceptable side effects.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Columbia University

Trial Keywords

  • Triple Negative
  • Basal-like

Last Updated

August 28, 2017